During primary virus infections, innate immune cells sense foreign molecules and, in turn alert and arm effector lymphocytes by secreting pro-inflammatory cytokines. Type I interferons (IFN-a/b) are a class of pro-inflammatory cytokines that are secreted by innate dendritic cells during virus infections. IFN-a/b is important in driving the development of human CD4+ T cells to secrete high levels of IFN-g that promotes the eradication of virally-infected cells. However, in mice, IFN-a/b does not promote the induction of IFN-g secretion from CD4+ T cells because the murine IFN-a/b receptor does not activate the critical down-stream transcription factor, STAT4, required to promote IFN-g secretion. This important pathway is blocked in mice and does not reflect the important role that CD4+ T cells play during virus infections in humans. Our lab has discovered the species-specific component for the human IFN-a/b receptor that promotes STAT4 activation in human CD4+ T cells. Therefore, the goals of this project are 1) To reconstitute IFN-a/b-dependent STAT4 signaling in murine T cells by genetic manipulation, and 2) Determine the role that this pathway plays during in vivo interferon responses in genetically altered mice. [unreadable] [unreadable] [unreadable]